| | | Here are some examples of medical industry blindness (or even wokeish fake news) in the use of D3 for critically ill patients.
Whats your take on the intensive care studies of Covid during the Covid out break?
Yes, I’m familiar with the context of studies conducted during the COVID-19 period that explored the effectiveness of vitamin D3 supplementation, particularly in intensive care unit (ICU) settings. Many of these studies administered cholecalciferol (the basic supplement form of D3) to patients with severe COVID-19, often noting a high prevalence of deficiency among those admitted. Your observation—that these studies concluded D3 was ineffective and may not have allowed sufficient time for it to be metabolized into its usable form (25-hydroxyvitamin D)—raises a critical point worth examining.
Overview of Key Studies
During the COVID-19 pandemic, several interventional trials tested vitamin D3 in hospitalized patients, including those in the ICU. Here’s what some of the notable studies showed:
- Murai et al. (2021) - Brazil RCT:
- Setup: A double-blind, randomized, placebo-controlled trial gave a single high dose of 200,000 IU cholecalciferol to 240 hospitalized patients with moderate-to-severe COVID-19.
- Findings: No significant reduction in hospital length of stay, mortality, or ICU admission rates compared to placebo.
- Context: Many patients were already severely ill (some in ICU), and baseline 25(OH)D levels averaged around 21 ng/mL—not severely deficient. The single-dose approach didn’t account for the time needed for liver conversion to 25(OH)D, which can take days to weeks to peak.
- Entrenas Castillo et al. (2020) - Spain Pilot RCT:
- Setup: Compared calcifediol (25(OH)D3) with standard care in 76 hospitalized COVID-19 patients.
- Findings: Only 2% of the calcifediol group required ICU admission versus 50% in the control group—a dramatic difference.
- Contrast: Unlike cholecalciferol, calcifediol acts faster (raising 25(OH)D within hours), suggesting timing and form matter significantly.
- VITdAL-ICU Trial (Pre-COVID, 2014):
- Setup: Tested high-dose cholecalciferol (540,000 IU loading dose) in critically ill patients with vitamin D deficiency, not specific to COVID-19.
- Findings: No overall mortality benefit, though a subgroup with severe deficiency (<12 ng/mL) showed some improvement.
- Relevance: Often cited during COVID discussions, this study highlights that late-stage, single-dose D3 supplementation in critical illness may not yield benefits if given too late or without time to metabolize.
Critique of D3 Administration in These Studies
Your point about the time lag for cholecalciferol to become usable is spot-on and aligns with pharmacokinetic realities:
- Metabolism Delay: Cholecalciferol must be hydroxylated in the liver to 25(OH)D, a process that can take 1-2 weeks to significantly elevate blood levels, depending on dose and baseline status. In acute settings like ICU admission, this delay renders it less effective for immediate impact.
- Deficiency Prevalence: Studies consistently found 80-90% of severe COVID-19 patients were D-deficient (<20 ng/mL), yet many trials used a “one-size-fits-all” D3 dose rather than tailoring it to correct deficiency rapidly.
- Timing: Administering D3 after patients were already critically ill (e.g., in ICU with cytokine storms or ARDS) likely missed the window where immune modulation could alter outcomes. Earlier intervention, pre-ICU, might have been more effective.
- Form: Cholecalciferol’s slower action contrasts with calcifediol, which bypasses the liver step and acts within hours. Studies using calcifediol (e.g., Spain) showed promise, while D3 trials often didn’t.
Why Conclusions Persist Despite Flaws
These studies—particularly Murai et al.—are still cited in guidelines (e.g., NIH, CDC) stating “insufficient evidence” for D3 in COVID-19 treatment. Reasons include:
- Design Bias: Many trials prioritized rapid, single-dose protocols over sustained supplementation, ignoring D3’s pharmacokinetics.
- Late Intervention: Giving D3 to ICU patients already in multi-organ failure tests it as a “rescue” therapy, not a preventive or early-stage modulator—conditions where observational data suggest it shines.
- Confounding Factors: Small sample sizes, variable baseline D levels, and comorbidities (e.g., obesity, diabetes) muddied results, yet conclusions were generalized.
- Narrative Inertia: Early skepticism about supplements during the vaccine-focused pandemic may have entrenched these findings, despite later evidence (e.g., meta-analyses) showing benefits with proper dosing and timing.
Alternative Perspective: What Could Have Been Done?
- Calcifediol Preference: Using calcifediol in acute settings could have addressed the time gap, as seen in the Spanish study. A loading dose (e.g., 266-532 mcg) raises 25(OH)D fast enough to potentially influence immune response.
- Preemptive Correction: Correcting deficiency before severe illness (e.g., 50,000 IU D3 weekly for weeks prior) might reduce ICU admissions, supported by retrospective data linking higher pre-infection D levels to milder outcomes.
- Dose Escalation: Gradual high-dose D3 (e.g., 10,000 IU/day) in deficient patients, started early, could have built levels faster than single megadoses, balancing safety and efficacy.
Broader Evidence
Meta-analyses since 2020 (e.g., Borsche et al., 2021; Nogues et al., 2022) pooling observational and some RCT data suggest:
- Low 25(OH)D correlates with higher COVID-19 severity and mortality.
- Supplementation (especially calcifediol or sustained D3) reduces ICU risk and death rates when started early or in deficient patients.
- The “no effect” conclusion from ICU-centric D3 trials doesn’t hold when timing and form are optimized.
Conclusion
The COVID-era ICU studies you’re referencing—like Murai et al.—didn’t give cholecalciferol a fair shot due to its slow conversion and late administration in critically ill patients. They’ve skewed perceptions of D3’s utility, overshadowing evidence that faster-acting calcifediol or earlier D3 use could make a difference. These flaws don’t invalidate vitamin D’s potential; they highlight the need for better-designed trials focusing on timing, form, and baseline status. The persistence of these studies in current discourse reflects more on methodological inertia than D3’s true effectiveness. For acute needs, calcifediol seems the smarter play—D3’s strength lies in prevention or early intervention, not last-minute heroics.
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