Which randomized trials have tested vitamin K2/D3 for long COVID and what were their outcomes?
Executive summary
A single randomized controlled trial published in Nutrients is, to date, the only randomized study that specifically tested combined vitamin K2 (MK‑7) and vitamin D3 for established long COVID and reported modest beneficial signals on symptoms and biological markers; the trial was single‑site, enrolled 151 participants, used a 2:1 randomization to active treatment versus standard of care, and ran for 24 weeks [1] [2]. Other randomized vitamin trials in the COVID literature have addressed acute infection or isolated vitamins but do not duplicate this long COVID K2/D3 intervention, leaving the Nutrients RCT as an important but not definitive piece of evidence [3] [4].
1. The trial that matters: University Hospitals Cleveland Medical Center randomized K2/D3 trial
The trial published January 16, 2025 in Nutrients was a single‑site randomized controlled clinical study at University Hospitals Cleveland Medical Center (UHCMC) that enrolled adults with at least two moderate long COVID symptoms persisting at least three months after infection and randomized 151 participants in a 2:1 ratio to daily co‑formulated vitamin K2 (240 µg MK‑7) plus vitamin D3 (50 µg / 2,000 IU) or standard of care for 24 weeks [1] [2]. The investigators hypothesized that attenuating systemic inflammation with K2/D3 would improve long COVID symptom burden and measured symptom indices along with markers of fungal translocation and inflammation [2] [1].
2. What the Nutrients trial reported: symptom and biomarker signals
Authors reported that the active treatment arm experienced a 7.1% decrease in the proportion of participants whose Long COVID Index exceeded the diagnostic threshold (>12), while the standard‑of‑care arm saw a 7.2% increase over the same period, and that the average number of long COVID symptoms remained stable in the vitamin K2/D3 arm but increased in the SOC arm—findings framed as beneficial signals for the intervention [5] [2]. The paper also highlights changes in measures of fungal translocation and systemic inflammation consistent with the proposed anti‑inflammatory mechanism, though full datasets and secondary endpoint details are available upon request from the corresponding author per the publication [1].
3. Study design, scale and disclosures that shape interpretation
Important contextual facts temper enthusiasm: the trial was single‑site and relatively small (151 participants with a 2:1 allocation), which limits generalizability and statistical power for subgroup or rare‑event analyses [1]. The study was designed and funded by University Hospitals, and the K2 ingredient (K2VITAL™ MCT) used in the trial was supplied by Balchem, a manufacturer with commercial interest in K2 products—details disclosed in press materials and company communications [6] [7]. The authors note IRB approval and trial registration (NCT05356936), and they make data available on request, which is standard but means independent replication and pooled meta‑analysis are still required [1].
4. How this trial fits into the broader vitamin‑COVID evidence landscape
Randomized trials of vitamin D (and of K2 in acute hospitalized COVID) exist but address different questions: several RCTs have tested vitamin D for prevention or outcomes in acute COVID, and a separate small phase‑2 double‑blind randomized trial examined K2 supplementation in hospitalized COVID‑19 patients, neither of which directly assesses long COVID symptom clusters or the K2/D3 combo in the post‑acute setting [4] [3]. Review and opinion pieces published earlier in the pandemic urged randomized trials of vitamins D and K (often together with magnesium) to verify observational signals linking vitamin status to COVID severity—calls that the Nutrients trial directly answered for long COVID but only on a preliminary scale [8] [9] [10].
5. Bottom line and what’s still unknown
The Nutrients randomized trial is the only randomized trial to specifically test combined vitamin K2 and D3 for long COVID and reports modest symptomatic and biomarker improvements over 24 weeks in a 151‑participant, single‑site study [1] [5]. The evidence should be read as promising but preliminary: replication in larger, multisite, placebo‑controlled trials, independent analyses of raw data, and longer follow‑up are required to establish clinical efficacy, rule out chance findings or site‑specific biases, and quantify who — if anyone — benefits most; the existing literature on D or K in acute COVID supports the biological plausibility but not definitive long COVID treatment guidance [3] [4] [8].