This following is a snapshot of his summary as of July 27
Caution on mega-doses doesn’t alter the facts or urgency of fixing low D
June 5, 2020 (updated July 8) Karl Pfleger, [email protected] (I declare no conflicts.)
There’s no reason not to fix low vitamin D & much evidence it could save many lives. Until the data becomes inconsistent with that possibility, fixing low D while getting more data must be prioritized.
Facts
- It’s widely agreed that low vitamin D (<30ng/ml) results in worse health & more deaths. 1,2,3,4
- Causal evidence shows D protects against respiratory infections (40 RCTs, n=30k) & lung injury.
- Low D is prevalent worldwide. USA: 40% D<20ng/ml, 64% healthy D<30. 96% nursing home D<30.
- D’s RDA was set 10x too low due to a mistake. 30ng/ml needs 6200 IU/day. Experts say raise RDA.
- D is safe: Toxicity unlikely <80ng/ml. 19 orgs say 4000 IU/day safe, Endocrine Society says 10,000.
- Many causal biological mechanisms argue D especially important against COVID-19. 1,2,3,4,5,6,7
- Calcitriol (active form vitD) has direct inhibitory effect on SARS-CoV-2 in human epithelial cells. 1
- Severe COVID-19 correlates strongly (eg, 3x likelier) w/ low D across many studies. 1,2,3,4,5,6,7
- Causal Inference Modeling & Mendelian Randomization show D’s effect on COVID-19 to be causal.
- 1st controlled trial: 1000 IU/d D +Mg&B12 group needed oxygen 6.5x less, adj. f/ age, sex, comorb.
Imperatives
- Hospitals & doctors should test the vitamin D blood level of all COVID-19 positive patients, and medical records holders should release analyses or datasets of D level vs case severity.
- COVID-19 standard-of-care should change to include testing & raising D levels (to >=30ng/ml), and care facilities should report differences in outcomes vs before doing so (as in fact #10 study).
- Governments should prioritize eradicating insufficient D (<30ng/ml) as a top priority for controlling the pandemic, alongside distancing & masks. This requires clear, widespread messaging & testing.
- The NAM, FDA, & analogs should increase recs (RDA/DV/etc) to 4000IU (0.1mg) until end of crisis.
- The FDA should require all COVID19 clinical trials (new & underway) to test D levels of all subjects. New trials should also treat D insufficiency in both arms to find efficacy in more than the D deprived.
Objections Dismissed
- Correlation isn’t causation: Facts 2,6,7,9,&10 are causal evidence very consistent w/ the other data.
- Experts urge caution / RCTs needed: Caution warnings apply only to mega-doses, for which RCTs would be needed. No one suggests anyone keep D levels too low. RCTs to fix low D are unethical.
- Preprints might be flawed: True, but when so much evidence is consistent, removing a few pieces wouldn’t change much. Authors of facts 7-10 preprints were vetted. 3 questionable preprints were omitted. Facts 1-5 plus any few of the 15+ new papers would be convincing enough. The biggest study from fact 8 is fully peer reviewed and accepted for publication.
- Some D supplement trials show no benefit: Most such trials have subjects with already sufficient D, use monthly mega-doses, use D2, or use doses too low to achieve sufficiency (see fact 4).
- Studies show D level not related to C19 infection rate 1,2: These studies used 10+ yr-old D tests & are contradicted by better studies w/ recent tests 3,4,5, w/ 3 biggest & peer reviewed. Also, trials showing no fewer infections do not cast doubt on the evidence for disease severity (facts 8-10).
Details - beyond the summary
His full analysis is here
Table of contents for it as of July 27:
Vitamin D facts from before COVID-19
Low D worsens many health issues including infections
D slows (worm) aging and predicts (human) all-cause mortality
D deficiency is widespread & itself considered a pandemic
The RDA for D was set 10x too low due to a math mistake
Moderate D supplementation has low risk
Blood tests for D level are easy, cheap, and widely available
COVID-19 and vitamin D related biology and data
Biological arguments suggest D usefulness for COVID-19
COVID-19 case severity correlates with low D status
Questionable studies correlating low D with case severity
Vitamin D is causally protective for COVID-19
COVID-19 infection risk correlates with low D status
Discussion
Correlational data supported by many pieces of causal evidence
Randomized trials for resolving D deficiency are unethical
Older adults may not be more D deficient broadly
Where are the COVID-19 cases with medium-to-high normal D?
Urgent, important questions
Reports claiming “no evidence”
Immediate recommendations
Practical considerations: testing, dose, & the sun is not enough
Conclusion
Related information in Vitamin D Life
COVID-19 and Vitamin D
COVID-19 news
COVID-19 recently updated files
COVID-19 and Dark Skins
Health problems at high risk of COVID-19