Vitamins K2 and D3 Improve Long COVID, Fungal Translocation, and Inflammation: [RCT], 2025, Atieh et al

Vitamins K2 and D3 Improve Long COVID, Fungal Translocation, and Inflammation: Randomized Controlled Trial

Ornina Atieh, Joviane Daher, Jared C Durieux, Marc Abboud, Danielle Labbato, Jhony Baissary, Ziad Koberssy, Kate Ailstock, Morgan Cummings, Nicholas T Funderburg, Grace A McComsey

Background
Long COVID (LC) is characterized by persistent symptoms at least 3 months after a SARS-COV-2 infection. LC has been associated with fungal translocation, gut dysfunction, and enhanced systemic inflammation. Currently, there is no approved treatment for this condition. The anti-inflammatory effect of vitamins K2 and D3 was shown to help attenuate the course of acute COVID-19 infection.

Objective and hypothesis
This trial aims to investigate the effects of vitamins K2/D3 on LC symptoms, as well as gut and inflammatory markers, in people with established long COVID. Our hypothesis is that by attenuating systemic inflammation, vitamins K2/D3 will improve long COVID symptoms.

Methods
This single-site randomized controlled study enrolled adults experiencing ≥2 moderate LC symptoms at least 3 months after a COVID-19 infection. The RECOVER Long COVID Research Index and number and type of LC symptoms were considered. Participants were randomized 2:1 to daily 240 µg K2 (pure MK-7 form) and 2000 UI vitamin D3 or standard of care (SOC) for 24 weeks. The endpoints were changes in symptomatology and in select inflammatory, metabolic, and gut biomarkers at 24 weeks.

Results
We enrolled 151 participants (n = 98 received vit K2/D3 and 53 received SOC). The median age was 46 years; 71% were female and 29% were non-white. Baseline demographics were balanced between groups. At 24 weeks, the active treatment group only had a sharp increase in 25(OH) D, indicating good treatment adherence. In the vitamin K2/D3 arm, there was a 7.1% decrease in the proportion who had an LC Index ≥12 (vs. a 7.2% increase in the SOC group; p = 0.01). The average number of LC symptoms remained stable in the vitamin K2/D3 arm but increased in the SOC arm (p = 0.03). Additionally, reductions in oxidized LDL, inflammatory markers sTNF-RI and sCD163, and fungal translocation marker (1,3)-β-d-glucan were observed in the vitamin K2/D3 arm compared to the SOC arm (p < 0.01) over 24 weeks.

Conclusions
Vitamins K2/D3 improved the RECOVER Long COVID Index, the number of LC symptoms, and several gut and inflammatory markers. Vitamins K2/D3 provide a promising safe intervention for people suffering from long COVID.

Link | PDF (Nutrients) [Open Access]

 

No placebo for controls:

 

I've been taking vitamin D and vitamin K2 (MK-7) daily for over a decade. I did recover from Covid infection without any lingering symptoms after a few months.

 

Not sure what to make of this.


I think I’d prefer plots of individual cases.

 

They pre-registered these outcomes:

• CRP*
• IL-6*
• Intestinal fatty acid binding protein (Ifab)*
• sTNF-RII*
• Vitamin D3 level
• Vitamin K2 level*
• Adverse events

They don't seem to report results for the starred markers, but they do report several markers they didn't pre-register.

I also don't see anything about multiple test adjustment.

Edit: Added star to sTNF-RII. They registered that, but reported results for sTNF-RI. (receptor 2 vs receptor 1)

Edit 2: Also nothing about K2 levels in the paper.

 

but

?

 

Selective reporting and a bit of data torture will get you a result.

 

Presentation of this study at CROI conference:

337 – Vitamins K2 and D3 Improve Long COVID Index, Fungal Translocation, and Inflammatory Biomarkers

Ornina Atieh, Jhony Baissary, Jared C. Durieux, Danielle Labbato, Marc Abboud, Ziad Koberssy, Joviane Daher, Kate Ailstock, Morgan Cummings, Nicholas Funderburg, Grace A. McComsey

Background
Long COVID (LC) is characterized by recurrent, prolonged, and new symptoms of COVID-19 at least 3 months after a SARS-COV-2 infection. LC was associated with fungal translocation, gut dysfunction, and enhanced inflammation. The anti-inflammatory vitamins K2/D3 were previously shown to reduce inflammation and help attenuate the course of acute COVID infection. This trial aims to investigate the effects of Vitamins K2/D3 on LC symptoms, gut markers and inflammatory markers in people with established long COVID.

Methods
This single-site randomized-controlled enrolled adults experiencing ≥2 moderate long COVID symptoms at least 3 months after COVID-19 infection. The RECOVER Long COVID index (JAMA 2023), number of LC symptoms, and resolution of symptoms were considered. Participants were randomized 2:1 to daily 240 µg K2 (pure MK-7 form) and 2000 UI Vitamin D3 or standard of care (SOC) for 24 weeks. Co-primary endpoints were changes in symptomatology and in select inflammatory markers at 24 weeks.

Results
We enrolled 151 participants (n=98 received vit K2/D3 and 53 standard of care). The median age was 46 years, 71% female and 29% non-white. Baseline demographics were balanced between groups. At 24 weeks, the active treatment group had a sharp increase in 25(OH) D indicating good treatment adherence, without change in the control arm. Vitamins K2/D3 arm showed a 3.2 (P=0.04) reduction in LC Index (P=0.04) and nearly two less (△ = -1.7; P=0.02) total number of LC symptoms compared to the SOC arm. Additionally, larger reductions in oxidized LDL, sTNF-RI, CD163, and the fungal translocation marker (1, 3)-β-d-glucan (BDG) were observed in the vitamins K2/D3 arm compared to the SOC arm (P<0.01). In adjusted models, vitamins K2/D3 randomization was associated with decreases in LC Index, but decreases in inflammatory markers and BDG were not. Decreases in BDG were associated with K2/D3 randomization and with decreases in inflammatory markers.

Conclusions
Vitamins K2/D3 improved Long COVID Index, number of LC symptoms, fungal translocation and several inflammatory markers. Vitamins K2/D3 provide a promising safe intervention for people suffering from long-COVID. Larger and longer studies are needed to assess the impact of this safe anti-inflammatory strategy.

Link (Conference on Retroviruses and Opportunistic Infections) [Abstract Only]