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Volume 18
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10.3390/nu18030521
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

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

by
Shinichiro Kodama
1,*,
Mitsuko Nakata
2,
Nafuko Konishi
3,
Masato Yoshino
4,
Akinori Fujisawa
5,
Mutsuo Naganuma
6,
Yuki Kobayashi
7,
Yuriko Hirai
8,
Akiko Kitagawa
9,
Mariko Miyokawa
9,
Ryo Mishima
10,
Satoshi Teramukai
2 and
Masanori Fukushima
11
1
Kodama Clinic, Hyogo 6650842, Japan
2
Departments of Biostatistics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan
3
Viola Clinic, Osaka 5300044, Japan
4
Kamata Yoshino Clinic, Tokyo 1440052, Japan
5
Honbetsu Cardiovascular Medicine Clinic, Hokkaido 0893314, Japan
6
Tokachi Mutsumino Clinic, Hokkaido 0800020, Japan
7
Kobayashi Clinic, Hyogo 6580048, Japan
8
MCL Corporation, Kyoto 6008191, Japan
9
Kitaris Co., Ltd., Aichi 4820018, Japan
10
The Clinical and Translational Research Center, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan
11
Foundation of Learning Health Society Institute, Nagoya 4500003, Japan
 
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Nutrients 2026, 18(3), 521; https://doi.org/10.3390/nu18030521
Submission received: 8 January 2026 / Revised: 29 January 2026 / Accepted: 30 January 2026 / Published: 3 February 2026
(This article belongs to the Section Micronutrients and Human Health)
Versions Notes

Abstract

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can develop as post-vaccination syndrome (PVS) or Post-Acute Sequelae of SARS-CoV-2 infection (PASC). In our prior retrospective study, most patients with PVS who developed ME/CFS had vitamin D insufficiency or deficiency. We evaluated the efficacy of vitamin D replacement therapy guidance for ME/CFS symptom improvement in patients with vitamin D insufficiency or deficiency. Methods: This open-label randomized controlled trial enrolled 91 participants with ME/CFS as PVS or PASC and serum 25(OH) vitamin D < 30 ng/mL across five clinical sites. Participants were randomized 1:1 to intervention (active vitamin D preparation plus vitamin D replacement therapy guidance: 25 μg daily supplementation, dietary counseling, sun exposure, and exercise) or control (active vitamin D preparation alone) for 12 weeks. The primary endpoint was the change in ME/CFS symptom count from screening to Week 12. Results: Mean symptom change was −6.7 in the intervention group versus −1.2 in the control group (between-group difference −5.6; 95% CI: −7.2, −3.9; p < 0.001). Serum 25(OH) vitamin D improved from 18.6 to 27.1 ng/mL in the intervention group, while the control group showed a decreasing trend (between-group difference 10.2 ng/mL; 95% CI: 7.9, 12.5). Achievement of <8 symptoms (i.e., no longer meeting ME/CFS diagnostic criteria) was significantly higher in the intervention group, with 16 participants achieving this threshold compared to 1 in the control group (p < 0.001). Subgroup analyses showed consistent benefit in both PVS (n = 56) and PASC (n = 29) cohorts. Conclusions: Vitamin D replacement therapy guidance significantly reduced ME/CFS symptoms along with improvement of serum 25(OH) vitamin D levels in patients with vitamin D insufficiency or deficiency who developed ME/CFS as PVS or PASC.
Keywords: COVID-19; post-vaccination syndrome; PASC; Long COVID; myalgic encephalomyelitis/chronic fatigue syndrome; vitamin D; COVID-19 vaccine COVID-19; post-vaccination syndrome; PASC; Long COVID; myalgic encephalomyelitis/chronic fatigue syndrome; vitamin D; COVID-19 vaccine

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MDPI and ACS Style

Kodama, S.; Nakata, M.; Konishi, N.; Yoshino, M.; Fujisawa, A.; Naganuma, M.; Kobayashi, Y.; Hirai, Y.; Kitagawa, A.; Miyokawa, M.; et al. Vitamin D in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome after COVID-19 or Vaccination: A Randomized Controlled Trial. Nutrients 2026, 18, 521. https://doi.org/10.3390/nu18030521

AMA Style

Kodama S, Nakata M, Konishi N, Yoshino M, Fujisawa A, Naganuma M, Kobayashi Y, Hirai Y, Kitagawa A, Miyokawa M, et al. Vitamin D in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome after COVID-19 or Vaccination: A Randomized Controlled Trial. Nutrients. 2026; 18(3):521. https://doi.org/10.3390/nu18030521

Chicago/Turabian Style

Kodama, Shinichiro, Mitsuko Nakata, Nafuko Konishi, Masato Yoshino, Akinori Fujisawa, Mutsuo Naganuma, Yuki Kobayashi, Yuriko Hirai, Akiko Kitagawa, Mariko Miyokawa, and et al. 2026. "Vitamin D in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome after COVID-19 or Vaccination: A Randomized Controlled Trial" Nutrients 18, no. 3: 521. https://doi.org/10.3390/nu18030521

APA Style

Kodama, S., Nakata, M., Konishi, N., Yoshino, M., Fujisawa, A., Naganuma, M., Kobayashi, Y., Hirai, Y., Kitagawa, A., Miyokawa, M., Mishima, R., Teramukai, S., & Fukushima, M. (2026). Vitamin D in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome after COVID-19 or Vaccination: A Randomized Controlled Trial. Nutrients, 18(3), 521. https://doi.org/10.3390/nu18030521

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