From Karl Pfleger’d LinkedIn:

Data from the new TargetD trial suggests that prior vitamin D trials were flawed.

Many people, even professionals, still think vitamin D was a false profit that was disproven by big RCTs. This view is very flawed, for several reasons. A brief history:

For decades, thousands of studies have shown reliable correlation of low vitamin D levels & bad health outcomes. Scientifically, the proper way to test the hypothesis that this correlation is causal is RCTs that meaningfully alter the low vitamin D status & then measure outcomes.

Heaney in 2014 published trial design guidelines for nutrients saying essentially the above.

Rule 4 was "The hypothesis to be tested must be that a change in nutrient status (not just a change in diet) produces the sought-for effect."

This trial design guideline was repeated in 2018 specifically for vitamin D by Grant et al. But almost every negative vitamin D trial violates these guidelines & fails to properly scientifically test the hypothesis.

In 2020 Boucher specifically & directly addressed this issue in a short paper, "Why do so many trials of vitamin D supplementation fail?"

Common simple D RCT flaws:
- Not starting w/ subjects w/ low levels.
- Not using high enough dose to meaningfully change status (eg resolve deficiency). Esp true w/ overweight subjects who need higher doses.
- Not waiting long enough for levels to rise before measuring outcomes.

Now a new trial called Target-D tries to do the right thing by repeatedly testing 25OHD until a prespecified target (40ng/ml) is achieved & early data presented at American Heart Association's Nov'23 meeting vindicates the criticisms of the prior trials.

Outcome data not mentioned (prob not avail yet) but data f/ early dosing still shows the issues:

On dose: "90% [of subjects] required some level of Vitamin D dosing. Of those, 86.5% required more than 2000 IU daily [VITAL study dose] and 14.6% required more than 10,000 IU daily"

On how long it took: "Less than 65% achieved over 40 ng/mL at three months. Another 25% of patients required six months or more of dosing titration" So longer than most D RCTs wait to measure outcomes, usually w/o testing levels achieved. Shows mid-trial testing is important.

"Our findings here show that just giving patients some Vit D does not help them achieve optimal levels"

Just b/c a trial is big doesn't mean it answers the right question. Most failed D trials don't negate the hypothesis that raising levels f/ low to sufficient improves health.