25-Hydroxyvitamin D (Vitamin D Status)

25-hydroxyvitamin D (25-OH-D) is the standard blood test for vitamin D status, measuring the storage form the liver produces from either sun exposure or dietary/supplemental vitamin D. The claim, widely repeated in wellness media: correcting low vitamin D reduces cancer, cardiovascular disease, and all-cause mortality, beyond its well-established role in bone health and calcium regulation.

The VITAL trial, a randomized controlled trial of 25,871 adults given 2,000 IU/day vitamin D3 or placebo for a median 5.3 years, found vitamin D did not significantly reduce the primary endpoint of total invasive cancer incidence (hazard ratio 0.96, 95% CI 0.88-1.06) or major cardiovascular events (HR 0.97, 95% CI 0.85-1.12), and did not reduce all-cause mortality (HR 0.99, 95% CI 0.87-1.12) [1]. It did show a promising signal for reduced cancer mortality (HR 0.83, 95% CI 0.67-1.02), which strengthened when analyses excluded the first one to two years of follow-up (HR 0.75, 95% CI 0.59-0.96), suggesting a possible latency effect for cancer-specific outcomes even without a broader mortality or cardiovascular benefit [1]. Updated meta-analyses incorporating VITAL and other large trials confirm a modest cancer-mortality signal without confirming cardiovascular or overall mortality benefit [2][4].

How to measure it: a standard blood draw measures 25-OH-D via immunoassay or liquid chromatography-mass spectrometry (LC-MS/MS), the latter considered the gold-standard reference method since some immunoassays cross-react inconsistently with vitamin D2 versus D3 forms. The Institute of Medicine/National Academies and most endocrine societies define deficiency as below 20 ng/mL (50 nmol/L) and sufficiency at or above 20-30 ng/mL, though the optimal target for non-skeletal benefits remains actively debated [3].

How to intervene on it: vitamin D3 (cholecalciferol) supplementation reliably raises 25-OH-D levels in a dose-dependent way; 1,000-2,000 IU/day typically raises levels by 10-20 ng/mL over 2-3 months in most adults, though individual response varies with body fat, baseline levels, and genetic factors affecting vitamin D binding protein [3]. Bryan Johnson's Blueprint protocol tracks 25-OH-D as one of its standard panel biomarkers, an n=1 self-report of routine supplementation to a targeted range rather than trial evidence [6].

Critics note much of the enthusiasm for vitamin D as a broad disease-prevention tool stemmed from observational studies where low vitamin D correlated with worse health outcomes, a pattern potentially explained by reverse causation, since sicker, less mobile people get less sun and have lower vitamin D, rather than vitamin D deficiency causing the disease. The VITAL trial and the D-Health trial in Australia have largely not confirmed the more sweeping observational claims, tempering expectations for supplementation beyond correcting frank deficiency [5].

The plain takeaway: vitamin D deficiency should be corrected for established reasons like bone health, and correcting it may offer a modest cancer-mortality benefit, but large randomized trials have not confirmed that vitamin D supplementation broadly prevents cancer, heart disease, or extends life in people who are not deficient to begin with.