Vitamin D in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome After COVID-19 or Vaccination: A Randomized Controlled Trial.

Vitamin D replacement therapy guidance significantly reduced ME/CFS symptom count compared to active vitamin D preparation alone over 12 weeks.

• Mean symptom change was -6.7 in the intervention group versus -1.2 in the control group.
• Between-group difference was -5.6 (95% CI: -7.2, -3.9; p < 0.001).
• The trial enrolled 91 participants randomized 1:1 to intervention or control.
• The intervention consisted of active vitamin D preparation plus guidance including 25 μg daily supplementation, dietary counseling, sun exposure, and exercise for 12 weeks.

Serum 25(OH) vitamin D levels improved substantially in the intervention group while showing a decreasing trend in the control group.

• Serum 25(OH) vitamin D improved from 18.6 to 27.1 ng/mL in the intervention group.
• The control group showed a decreasing trend in serum 25(OH) vitamin D.
• Between-group difference in serum 25(OH) vitamin D was 10.2 ng/mL (95% CI: 7.9, 12.5).
• All enrolled participants had baseline serum 25(OH) vitamin D < 30 ng/mL at screening.

Significantly more participants in the intervention group no longer met ME/CFS diagnostic criteria at Week 12.

• Achievement of fewer than 8 symptoms (i.e., no longer meeting ME/CFS diagnostic criteria) was significantly higher in the intervention group.
• 16 participants in the intervention group achieved this threshold compared to 1 in the control group (p < 0.001).

Subgroup analyses showed consistent benefit of the intervention in both post-vaccination syndrome and post-acute sequelae of SARS-CoV-2 infection cohorts.

• The PVS subgroup included 56 participants and the PASC subgroup included 29 participants.
• Both subgroups showed consistent benefit from the intervention.
• ME/CFS can develop as post-vaccination syndrome (PVS) or Post-Acute Sequelae of SARS-CoV-2 infection (PASC).

In a prior retrospective study by the authors, most patients with post-vaccination syndrome who developed ME/CFS had vitamin D insufficiency or deficiency.

• This prior finding motivated the current randomized controlled trial.
• The trial enrolled participants with serum 25(OH) vitamin D < 30 ng/mL, corresponding to vitamin D insufficiency or deficiency.
• The trial was conducted across five clinical sites.

The trial was designed as an open-label randomized controlled trial with a 1:1 allocation ratio.

• 91 participants were enrolled with ME/CFS as PVS or PASC and serum 25(OH) vitamin D < 30 ng/mL.
• Participants were randomized 1:1 to intervention or control.
• The intervention group received active vitamin D preparation plus vitamin D replacement therapy guidance (25 μg daily supplementation, dietary counseling, sun exposure, and exercise).
• The control group received active vitamin D preparation alone.
• The primary endpoint was the change in ME/CFS symptom count from screening to Week 12.